Novel pseudoceramide compound and production method for same

ABSTRACT

The present invention provides: a novel pseudoceramide compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof. The present invention has a skin protecting effect in that the invention has a superior effect in skin moisturisation and is outstandingly stable and soluble, and thus the invention can protect the skin from external irritation without side effects, and can be used as an active substance in damaged skin recovery and prevention. Consequently, the invention can be used as a skin-moisturising dermatological external composition, cosmetic composition or pharmaceutical composition.

TECHNICAL FIELD

The present disclosure relates to a novel pseudo-ceramide compound and amethod for preparing same. More particularly, the present disclosurerelates to a novel pseudo-ceramide compound as atris(hydroxymethyl)aminomethane derivative, an isomer thereof, apharmaceutically acceptable salt thereof, a prodrug thereof, a hydratethereof or a solvate thereof and a method for preparing same.

BACKGROUND ART

Ceramides are one of the main components of the intercellular lipidswhich constitute the stratum corneum of the skin and serve to preventexcessive water loss due to evaporation and maintain the structure ofthe stratum corneum. The stratum corneum serves as a barrier to protectunderlying tissue from harmful substances or microorganisms from theexternal environment. When differentiated keratinocytes shed from thestratum corneum, the intercellular lipids of the stratum corneum form alamellar structure, thereby contributing to maintenance of the skin'sbasic function. The intercellular lipids consist of ceramide,cholesterol, free fatty acid, etc. and, among them, ceramide is known toplay a key role in water retention and barrier function of the stratumcorneum. A decreased ceramide content in the stratum corneum is known toresult in increased evaporation of water and aggravation of various skindiseases. Also, it is known that the skin with decreased ceramidecontent in the stratum corneum caused by skin aging or externalstimulation can be recovered to normal state by supplementing ceramidefrom outside. Accordingly, studies have been conducted on variousnatural animal and plant products containing ceramides. However, naturalceramide is difficult to be produced in large scale because ofdifficulty in extraction, etc. and is inappropriate forcommercialization due to high cost. In addition, natural ceramide islimited in exhibiting efficacy since its content in cosmetic products isrestricted because of low solubility in various solvents. Therefore,research and development of pseudo-ceramides mimicking naturallyoccurring ceramide and having improved physical properties, which canresolve the disadvantage of natural ceramide and can be commercialized,is necessary.

REFERENCES OF THE RELATED ART Patent Documents

Korean Patent Publication No. 10-2010-0001374

DISCLOSURE Technical Problem

The present disclosure is directed to providing a novel pseudo-ceramidecompound having improved stability, solubility and skin moisturizingability, wherein a fatty acid is introduced totris(hydroxymethyl)aminomethane, and a method for preparing same.

Technical Solution

In a general aspect, there is provided a novel pseudo-ceramide compoundrepresented by Chemical Formula 1, an isomer thereof, a pharmaceuticallyacceptable salt thereof, a prodrug thereof, a hydrate thereof or asolvate thereof:

wherein each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.

In an exemplary embodiment of the present disclosure, each of R₁ and R₂may be independently a C₁₁-C₁₇ saturated or unsaturated aliphatic chainunsubstituted or substituted with a hydroxyl group.

In an exemplary embodiment of the present disclosure, each of R₁ and R₂may be independently selected from a group consisting of C₁₁H₂₃, C₁₃H₂₇,C₁₅H₃₁, C₁₇H₃₅, C₁₇H₃₁ and C₁₇H₃₃.

In an exemplary embodiment of the present disclosure, thepseudo-ceramide compound, isomer thereof, pharmaceutically acceptablesalt thereof, prodrug thereof, hydrate thereof or solvate thereof may betris(hydroxymethyl)aminomethane substituted with a fatty acid.

In an exemplary embodiment of the present disclosure, thepseudo-ceramide compound, isomer thereof, pharmaceutically acceptablesalt thereof, prodrug thereof, hydrate thereof or solvate thereof may beselected from a group consisting of hexadecanoic acid2-hexadecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester, dodecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,tetradecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, octadecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, octadecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,octadecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, dodecanoicacid 3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester,octadec-9-enoic acid3-hydroxy-2-hydroxymethyl-2-octadec-9-enoylamino-propyl ester,octadeca-9,12-dienoic acid3-hydroxy-2-hydroxymethyl-2-octadeca-9,12-dienoylamino-propyl ester,10-hydroxy-dec-2-enoic acid3-hydroxy-2-(10-hydroxy-dec-2-enoylamino)-2-hydroxymethyl-propyl ester,10-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(10-hydroxy-octadecanoylamino)-propyl ester,12-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(12-hydroxy-octadecanoylamino)-propyl esterand 16-hydroxy-hexadecanoic acid3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester.

In another general aspect, there is provided a method for preparing thenovel pseudo-ceramide compound, isomer thereof, pharmaceuticallyacceptable salt thereof, prodrug thereof, hydrate thereof or solvatethereof, including reacting tris(hydroxymethyl)aminomethane and a fattyacid compound under a basic condition to synthesize a pseudo-ceramidecompound.

In an exemplary embodiment of the present disclosure, the method may berepresented by Scheme 1:

wherein each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.

In another general aspect, there is provided a composition formoisturizing skin, including the novel pseudo-ceramide compound, isomerthereof, pharmaceutically acceptable salt thereof, prodrug thereof,hydrate thereof or solvate thereof as an active ingredient.

In an exemplary embodiment of the present disclosure, the activeingredient may be included in an amount of 0.01-20 wt % based on thetotal weight of the composition.

In an exemplary embodiment of the present disclosure, the compositionmay be a composition for external application to skin.

In an exemplary embodiment of the present disclosure, composition may bea cosmetic composition or a pharmaceutical composition.

Advantageous Effects

Since the novel pseudo-ceramide compound of the present disclosure issuperior in stability, solubility and skin moisturizing effect, it canbe used as an active ingredient for protecting the skin from externalstimulation and recovering or preventing damage to the skin without sideeffects. Accordingly, it can be used in a composition for externalapplication to skin, a cosmetic composition or a pharmaceuticalcomposition for moisturizing the skin.

DESCRIPTION OF DRAWINGS

FIG. 1 shows change in transepithelial electrical resistance upontreatment with a pseudo-ceramide compound according to an exemplaryembodiment of the present disclosure.

FIG. 2 shows a quantitative analysis result of ceramides in artificialskin upon treatment with a pseudo-ceramide compound according to anexemplary embodiment of the present disclosure.

BEST MODE

Hereinafter, exemplary embodiments of the present disclosure will bedescribed in detail so that those of ordinary skill in the art to whichthe present disclosure belongs can easily carry out the presentdisclosure.

As used herein, “skin” means the tissue covering the body surface of ananimal and is used in the broadest sense, including not only the tissuecovering the surface of face or body but also the scalp and hair.

As used herein, “pharmaceutically acceptable” means being devoid ofsubstantial toxic effects when used in a usually employed medicinaldosage and thereby being approvable or approved by the government or aninternational organization comparable thereto for use in animals, andmore particularly in humans, or being listed in the pharmacopeia.

As used herein, “pharmaceutically acceptable salt” refers to a saltaccording to an aspect of the present disclosure that ispharmaceutically acceptable and possesses the desired pharmacologicalactivity of the parent compound. Such salts include: (1) acid additionsalts formed with inorganic acids such as hydrochloric acid, hydrobromicacid, sulfuric acid, nitric acid, phosphoric acid, etc. or formed withorganic acids such as acetic acid, propionic acid, hexanoic acid,cyclopentylpropionic acid, glycolic acid, pyruvic acid, lactic acid,malonic acid, succinic acid, malic acid, maleic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) benzoicacid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonicacid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid,benzenesulfonic acid, 4-chlorobenzenesulfonic acid,2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonicacid, 4-methylbicyclo[2,2,2]-oct-2-ene-1-carboxylic acid, glucoheptonicacid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylaceticacid, lauryl sulfuric acid, gluconic acid, glutamic acid,hydroxynaphthoic acid, salicylic acid, stearic acid and muconic acid; or(2) salts formed when an acidic proton present in the parent compound isreplaced.

As used herein, “prodrug” refers to a drug whose physical and chemicalproperties have been changed chemically such that it does not exhibit aphysiological activity as it is but is converted to an active drugthrough chemical or enzymatic processes after being administered.

As used herein, “hydrate” refers to a compound to which water is bound.The binding between water and the compound includes non-covalentbinding.

As used herein, “solvate” refers to a complex formed by a solutemolecule or ion and a solvent molecule or ion.

As used herein, “isomers” refers to compounds of the present disclosureor salts thereof with the same chemical formula or molecular formula butdifferent optical or steric properties.

Unless specified otherwise, the term “compound according to the presentdisclosure” or “compound represented by Chemical Formula 1” includes thecompound itself, a pharmaceutically acceptable salt thereof, a hydratethereof, a solvate thereof, an isomer thereof and a prodrug thereof.

The present disclosure provides a novel pseudo-ceramide compoundrepresented by Chemical Formula 1, an isomer thereof, a pharmaceuticallyacceptable salt thereof, a prodrug thereof, a hydrate thereof or asolvate thereof:

wherein each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.

Each of R₁ and R₂ is a C₉-C₂₃ saturated or unsaturated aliphatic chainor a C₉-C₂₃ saturated or unsaturated aliphatic chain having a hydroxylgroup. R₁ and R₂ may be the same or different from each other.

Specifically, each of R₁ and R₂ may be independently a C₁₁-C₁₇ saturatedor unsaturated aliphatic chain. More specifically, each of R₁ and R₂ maybe independently selected from a group consisting of a C₁₁H₂₃, C₁₃H₂₇,C₁₅H₃₁ or C₁₇H₃₅ saturated aliphatic chain and a C₁₇H₃₁ or C₁₇H₃₃unsaturated aliphatic chain.

The pseudo-ceramide compound according to the present disclosure has anamide moiety and an ester moiety in one molecule and has various fattyacid derivatives substituted therein. It may betris(hydroxymethyl)aminomethane substituted with a saturated orunsaturated fatty acid.

The pseudo-ceramide compound according to the present disclosure may beprepared by a method including reacting tris(hydroxymethyl)aminomethaneand a fatty acid compound under a basic condition using triethylamine tosynthesize a pseudo-ceramide compound.

A method for preparing the pseudo-ceramide compound according to thepresent disclosure may be schematically represented by Scheme 1. That isto say, tris(hydroxymethyl)aminomethane may be reacted with 1 equivalentof a fatty acid compound having R₁ and 1 equivalent of a fatty acidcompound having R₂ to synthesize the pseudo-ceramide compoundrepresented by Chemical Formula 1.

In Scheme 1, each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.

The pseudo-ceramide compound according to the present disclosure may beselected from a group consisting of hexadecanoic acid2-hexadecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester, dodecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,tetradecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, octadecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, octadecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,octadecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, dodecanoicacid 3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester,octadec-9-enoic acid3-hydroxy-2-hydroxymethyl-2-octadec-9-enoylamino-propyl ester,octadeca-9,12-dienoic acid3-hydroxy-2-hydroxymethyl-2-octadeca-9,12-dienoylamino-propyl ester,10-hydroxy-dec-2-enoic acid3-hydroxy-2-(10-hydroxy-dec-2-enoylamino)-2-hydroxymethyl-propyl ester,10-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(10-hydroxy-octadecanoylamino)-propyl ester,12-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(12-hydroxy-octadecanoylamino)-propyl esterand 16-hydroxy-hexadecanoic acid3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester,although not particularly being limited thereto.

The pseudo-ceramide compound according to the present disclosureexhibits excellent skin moisturizing effect while having superiorstability and solubility.

Accordingly, the present disclosure provides a composition formoisturizing skin, including the pseudo-ceramide compound, an isomerthereof, a pharmaceutically acceptable salt thereof, a prodrug thereof,a hydrate thereof or a solvate thereof as an active ingredient.

In the composition of the present disclosure, the active ingredient maybe included in an amount of 0.01-20 wt %, specifically 0.1-10 wt %, morespecifically 0.5-5 wt %, based on the total weight of the composition.When the active ingredient is included in an amount in theabove-described range, the effect desired by the present disclosure canbe adequately achieved while ensuring both stability and solubility ofthe composition and providing good cost effectiveness. Specifically, ifthe content of the pseudo-ceramide compound, an isomer thereof, apharmaceutically acceptable salt thereof, a prodrug thereof, a hydratethereof or a solvate thereof is less than 0.01 wt %, a sufficient skinmoisturizing effect may not be achieved. And, if it exceeds 20 wt %,cost effectiveness may be unsatisfactory.

The present disclosure also provides a composition for externalapplication to skin, including the pseudo-ceramide compound, an isomerthereof, a pharmaceutically acceptable salt thereof, a prodrug thereof,a hydrate thereof or a solvate thereof as an active ingredient.

The present disclosure also provides a cosmetic composition, includingthe pseudo-ceramide compound, an isomer thereof, a pharmaceuticallyacceptable salt thereof, a prodrug thereof, a hydrate thereof or asolvate thereof as an active ingredient.

The cosmetic composition according to the present disclosure may beprovided in the form of any formulation suitable for topicalapplication. For example, it may be provided in the form of solution,oil-in-water emulsion, water-in-oil emulsion, suspension, solid, gel,powder, paste, foam or aerosol. These formulations can be preparedaccording to the methods commonly employed in the art.

The cosmetic composition according to the present disclosure may furtherinclude other ingredients providing synergic effect without negativelyaffecting the desired effect. Specifically, the cosmetic compositionaccording to the present disclosure may further include arbutin andascorbic acid derivatives which may provide skin whitening effect. Inaddition, the cosmetic composition according to the present disclosuremay further include a moisturizing agent, an emollient agent, asurfactant, a UV absorbent, an antiseptic, a sterilizer, an antioxidant,a pH adjusting agent, an organic or inorganic pigment, a flavor, acooling agent or an antiperspirant. The contents of those ingredientsmay be easily determined by those skilled in the art within the rangesnot deteriorating the purpose and effect of the present disclosure. Theymay be included in an amount of 0.01-5 wt %, specifically 0.01-3 wt %,based on the total weight of the composition.

The present disclosure also provides a pharmaceutical compositionincluding the compound, an isomer thereof, a pharmaceutically acceptablesalt thereof, a prodrug thereof, a hydrate thereof or a solvate thereofas an active ingredient. The pharmaceutical composition may exhibitexcellent skin moisturizing effect.

The pharmaceutical composition according to the present disclosure maybe administered orally or parenterally, e.g., rectally, topically,transdermally, intravenously, intramuscularly, intraperitoneally,subcutaneously, etc. Formulations for oral administration may includetablet, pill, soft or hard capsule, granule, powder, fine granule,liquid, emulsion or pellet, although not being limited thereto.Formulations for parenteral administration may include solution,suspension, emulsion, gel, injectable solution, drip, suppository, patchor spray, although not being limited thereto. These formulations may beprepared easily according to the methods commonly employed in the artand may include a surfactant, an excipient, a hydrating agent, anemulsifier, a suspending agent, a salt or buffer for adjusting osmoticpressure, a coloring agent, a flavor, a stabilizer, an antiseptic, apreservative or other commonly used adjuvants, if desired.

Determination of the administration dose of the active ingredient iswithin the level of those skilled in the art. Although a dailyadministration dose may be varied with the severity and stage of thecondition to be treated, age and physical condition of a subject to betreated, presence of complication(s), or the like, the composition maybe administered with a daily dose of 1 μg/kg to 200 mg/kg, specifically50 μg/kg to 50 mg/kg, once to three times a day. However, the scope ofthe present disclosure is not limited by the above administration doseby any means.

Hereinafter, the present disclosure will be described in detail throughexamples. However, the following examples are for illustrative purposesonly and it will be apparent to those of ordinary skill in the art thatthe scope of the present disclosure is not limited by the examples.

Example 1 Preparation of hexadecanoic acid2-hexadecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),palmitoyl chloride (22.6 g, 1 eq) was slowly added dropwise for 30minutes while stirring at room temperature. After stirring for 2 hoursat room temperature, palmitoyl chloride (22.6 g, 1 eq) was slowly addeddropwise for 30 minutes and the mixture was further stirred for 6 hours.Upon completion of reaction, the mixture was diluted with ethyl acetate(200 mL) and washed with 1 N HCl solution (200 mL) and distilled water(200 mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 30 g of whitesolid (60%) was obtained using a silica column. The obtained white solidwas hexadecanoic acid2-hexadecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester representedby Chemical Formula 2. ¹H NMR analysis result of the white solid is asfollows.

¹H NMR (300 MHz, DMSO-d₆) 6.23 (br, 1H), 4.29 (s, 2H), 4.22 (t, J=6.6Hz, 2H), 3.70-3.64 (m, 2H), 3.54-3.48 (m, 2H), 2.36 (t, J=7.5 Hz, 2H),2.22 (t, J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 48H), 0.90-0.85(m, 6H).

Example 2 Preparation of dodecanoic acid2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),lauroyl chloride (18.0 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, lauroyl chloride (18.0 g, 1 eq) was slowly added dropwisefor 30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 26 g of whitesolid (65%) was obtained using a silica column. The obtained white solidwas dodecanoic acid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propylester represented by Chemical Formula 3. ¹H NMR analysis result of thewhite solid is as follows.

¹H NMR (300 MHz, DMSO-d₆) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.68-3.64 (m, 2H), 3.52-3.48 (m, 2H), 2.36 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 32H), 0.90-0.85 (m, 6H).

Example 3 Preparation of tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),myristoyl chloride (20.3 g, 1 eq) was slowly added dropwise for 30minutes while stirring at room temperature. After stirring for 2 hoursat room temperature, myristoyl chloride (20.3 g, 1 eq) was slowly addeddropwise for 30 minutes and the mixture was further stirred for 6 hours.Upon completion of reaction, the mixture was diluted with ethyl acetate(200 mL) and washed with 1 N HCl solution (200 mL) and distilled water(200 mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 38 g of whitesolid (63%) was obtained using a silica column. The obtained white solidwas tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propyl ester representedby Chemical Formula 4. ¹H NMR analysis result of the white solid is asfollows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.68-3.64 (m, 2H), 3.52-3.49 (m, 2H), 2.36 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 40H), 0.90-0.86 (m, 6H).

Example 4 Preparation of octadecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),stearoyl chloride (25 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, stearoyl chloride (25 g, 1 eq) was slowly added dropwisefor 30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 20 g of whitesolid (37%) was obtained using a silica column. The obtained white solidwas octadecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester representedby Chemical Formula 5. ¹H NMR analysis result of the white solid is asfollows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.53-3.49 (m, 2H), 2.36 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 56H), 0.90-0.86 (m, 6H).

Example 5 Preparation of octadecanoic acid2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester

The obtained white solid was octadecanoic acid2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester represented byChemical Formula 6. ¹H NMR analysis result of the white solid is asfollows.

¹H NMR (300 MHz, DMSO-d₆) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.53-3.50 (m, 2H), 2.36 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 44H), 0.90-0.86 (m, 6H).

Example 6 Preparation of octadecanoic acid3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),myristoyl chloride (21 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, stearoyl chloride (25 g, 1 eq) was slowly added dropwisefor 30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 20 g of whitesolid (40%) was obtained using a silica column. The obtained white solidwas octadecanoic acid3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propyl ester representedby Chemical Formula 7. ¹H NMR analysis result of the white solid is asfollows.

¹H NMR (300 MHz, CDCl₃) 6.22 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.53-3.49 (m, 2H), 2.37 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 48H), 0.90-0.86 (m, 6H).

Example 7 Preparation of tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),stearoyl chloride (25 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, myristoyl chloride (21 g, 1 eq) was slowly added dropwisefor 30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 22 g of whitesolid (45%) was obtained using a silica column. The obtained white solidwas tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester representedby Chemical Formula 8. ¹H NMR analysis result of the white solid is asfollows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.53-3.49 (m, 2H), 2.37 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 48H), 0.90-0.86 (m, 6H).

Example 8 Preparation of dodecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),stearoyl chloride (25 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, lauroyl chloride (18 g, 1 eq) was slowly added dropwise for30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 24 g of whitesolid (51%) was obtained using a silica column. The obtained white solidwas dodecanoic acid 3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propylester represented by Chemical Formula 9. ¹H NMR analysis result of thewhite solid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.53-3.49 (m, 2H), 2.37 (t, J=7.5 Hz, 2H), 2.22 (t,J=7.5 Hz, 2H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 44H), 0.90-0.86 (m, 6H).

Example 9 Preparation of octadec-9-enoic acid3-hydroxy-2-hydroxymethyl-2-octadec-9-enoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),oleyl chloride (25 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, oleyl chloride (25 g, 1 eq) was slowly added dropwise for30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 21 g of whitesolid (39%) was obtained using a silica column. The obtained white solidwas octadec-9-enoic acid3-hydroxy-2-hydroxymethyl-2-octadec-9-enoylamino-propyl esterrepresented by Chemical Formula 10. ¹H NMR analysis result of the whitesolid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 5.42-5.34 (m, 4H), 4.29 (s, 2H),4.18-4.14 (m, 2H), 3.69-3.65 (m, 2H), 3.53-3.49 (m, 2H), 2.40-1.90 (m,12H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 38H), 0.90-0.86 (m, 6H).

Example 10 Preparation of octadeca-9,12-dienoic acid3-hydroxy-2-hydroxymethyl-2-octadeca-9,12-dienoylamino-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding triethylamine (23 mL, 2 eq),linoleyl chloride (25 g, 1 eq) was slowly added dropwise for 30 minuteswhile stirring at room temperature. After stirring for 2 hours at roomtemperature, linoleyl chloride (25 g, 1 eq) was slowly added dropwisefor 30 minutes and the mixture was further stirred for 6 hours. Uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 18 g of whitesolid (33%) was obtained using a silica column. The obtained white solidwas octadeca-9,12-dienoic acid3-hydroxy-2-hydroxymethyl-2-octadeca-9,12-dienoylamino-propyl esterrepresented by Chemical Formula 11. ¹H NMR analysis result of the whitesolid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 5.50-5.20 (m, 8H), 4.29 (s, 2H),4.18-4.14 (m, 2H), 3.69-3.65 (m, 2H), 3.53-3.49 (m, 2H), 2.90-2.70 (m,4H), 2.40-1.90 (m, 12H), 1.62-1.60 (m, 4H), 1.42-1.11 (m, 28H),0.90-0.86 (m, 6H).

Example 11 Preparation of 10-hydroxy-dec-2-enoic acid3-hydroxy-2-(10-hydroxy-dec-2-enoylamino)-2-hydroxymethyl-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding dicyclohexylcarbodiimide (34g, 2 eq) and 4-dimethylaminopyridine (4.03 g, 0.2 eq),10-hydroxy-2-decanoic acid (30.7 g, 2 eq) was slowly added dropwise for30 minutes while stirring at room temperature. After stirring for 6hours, upon completion of reaction, the mixture was diluted with ethylacetate (200 mL) and washed with 1 N HCl solution (200 mL) and distilledwater (200 mL). The organic layer was dried with anhydrous magnesiumsulfate, filtered and concentrated under reduced pressure. Then, 15 g ofwhite solid (39%) was obtained using a silica column. The obtained whitesolid was 10-hydroxy-dec-2-enoic acid3-hydroxy-2-(10-hydroxy-dec-2-enoylamino)-2-hydroxymethyl-propyl esterrepresented by Chemical Formula 12. ¹H NMR analysis result of the whitesolid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.83-6.50 (m, 2H), 6.21 (s, 1H), 5.70-5.50 (m,2H), 4.29 (s, 2H), 4.18-4.14 (m, 2H), 3.69-3.65 (m, 2H), 3.53-3.49 (m,6H), 2.4-1.80 (m, 26H).

Example 12 Preparation of 10-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(10-hydroxy-octadecanoylamino)-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding dicyclohexylcarbodiimide (34g, 2 eq) and 4-dimethylaminopyridine (4.03 g, 0.2 eq), 10-hydroxystearicacid (49.5 g, 2 eq) was slowly added dropwise for 30 minutes whilestirring at room temperature. After stirring for 6 hours, uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 14 g of whitesolid (39%) was obtained using a silica column. The obtained white solidwas 10-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(10-hydroxy-octadecanoylamino)-propyl esterrepresented by Chemical Formula 13. ¹H NMR analysis result of the whitesolid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.60-3.53 (m, 2H), 3.53-3.49 (m, 2H), 2.37 (t, J=7.5Hz, 2H), 2.22 (t, J=7.5 Hz, 2H), 1.62-1.11 (m, 54H), 0.90-0.86 (m, 6H).

Example 13 Preparation of 12-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(12-hydroxy-octadecanoylamino)-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding dicyclohexylcarbodiimide (34g, 2 eq) and 4-dimethylaminopyridine (4.03 g, 0.2 eq), 12-hydroxystearicacid (49.5 g, 2 eq) was slowly added dropwise for 30 minutes whilestirring at room temperature. After stirring for 6 hours, uponcompletion of reaction, the mixture was diluted with ethyl acetate (200mL) and washed with 1 N HCl solution (200 mL) and distilled water (200mL). The organic layer was dried with anhydrous magnesium sulfate,filtered and concentrated under reduced pressure. Then, 12 g of whitesolid (32%) was obtained using a silica column. The obtained white solidwas 12-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(12-hydroxy-octadecanoylamino)-propyl esterrepresented by Chemical Formula 14. ¹H NMR analysis result of the whitesolid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.65 (m, 2H), 3.60-3.52 (m, 2H), 3.53-3.48 (m, 2H), 2.37 (t, J=7.5Hz, 2H), 2.22 (t, J=7.5 Hz, 2H), 1.62-1.11 (m, 54H), 0.90-0.86 (m, 6H).

Example 14 Preparation of 16-hydroxy-hexadecanoic acid3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester

Tris(hydroxymethyl)aminomethane (10 g, 1 eq) was dissolved indimethylformaldehyde (100 mL). After adding dicyclohexylcarbodiimide (34g, 2 eq) and 4-dimethylaminopyridine (4.03 g, 0.2 eq),16-hydroxydodecanoic acid (44.9 g, 2 eq) was slowly added dropwise for30 minutes while stirring at room temperature. After stirring for 6hours, upon completion of reaction, the mixture was diluted with ethylacetate (200 mL) and washed with 1 N HCl solution (200 mL) and distilledwater (200 mL). The organic layer was dried with anhydrous magnesiumsulfate, filtered and concentrated under reduced pressure. Then, 17 g ofwhite solid (45%) was obtained using a silica column. The obtained whitesolid was 16-hydroxy-hexadecanoic acid3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl esterrepresented by Chemical Formula 15. ¹H NMR analysis result of the whitesolid is as follows.

¹H NMR (300 MHz, CDCl₃) 6.21 (s, 1H), 4.29 (s, 2H), 4.18-4.14 (m, 2H),3.69-3.64 (m, 6H), 3.60-3.52 (m, 2H), 3.53-3.48 (m, 2H), 2.37 (t, J=7.5Hz, 2H), 2.22 (t, J=7.5 Hz, 2H), 1.60-1.54 (m, 12H), 1.30-1.20 (m, 40H).

Test Example 1 Recovery of Damaged Artificial Skin (Measurement ofTransepithelial Electrical Resistance)

Transepithelial electrical resistance was measured in order to testrecovery of damaged artificial skin by the compound of Example 2.Dodecanoic acid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl esterobtained from the Example 2 and phosphate buffered saline (PBS), octylmethoxycinnamate (OMC) and PC-104 were tested for comparison.

Transepithelial electrical resistance (TEER) of Keraskin™ purchased fromMCTT was measured after 22 hours of pre-incubation. After placing theKeraskin™ on a 6-well plate, 400 μL of a medium was added in an insertand 5 mL of the medium was added outside the insert such that an evenlevel was achieved inside and outside the insert. Then, measurement wasmade with the electrode tips of a resistance meter inside and outsidethe insert. TEER was measured for all the inserts, prior to the test,after treatment with the substances of Example 2 and ComparativeExamples 1-3 and 24 hours after post-incubation. The TEER after thepost-incubation was divided by the initial value to calculate the changein %. The result is shown in Table 1 and FIG. 1.

TABLE 1 Change of Test groups TEER (%) Comparative Example 1 [phosphate125.4 buffered saline (PBS)] Comparative Example 2 [octyl 30.9methoxycinnamate (OMC)] Comparative Example 3 (PC-104) 35.7 Example 270.8

As can be seen from Table 1, when transepithelial electrical resistancewas measured after treatment with the compound of Example 2, the effectof recovering damaged artificial skin was higher than the conventionallyused PC-104.

Test Example 2 Quantitative analysis of ceramide in artificial skin

Artificial skin was weighed and put in a 4-mL glass vial. After adding2400 μL of CHCl₃/MeOH (=½) and 100 μL of IS STD, the artificial skin wascut into small pieces with scissors. After sonication for 30 minutes,solutions mixing sodium lauryl sulfate (SLS) to each of dodecanoic acid2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester obtained fromthe Example 2, phosphate buffered saline (PBS), octyl methoxycinnamate(OMC) and PC-104, as described in Table 2, were filtered through a PTFEsyringe filter, and 1250 μL of each filtrate was transferred to an EPtube.

After completely removing the solvent using a speed vacuum dryer, theresidue was redissolved by adding 100 μL of an analytical mobile phase.After centrifugation, only the supernatant was taken and analyzed aftertransferring to an LC vial. The concentration of ceramide was correctedfor the weight of the artificial skin. The result is shown in Table 2and FIG. 2.

TABLE 2 Test groups C18SM ng/mg skin PBS + OMC 1747.3 990.8 SLS + OMC843.6 758.3 SLS + PC-104 1141.1 995.5 SLS + Example 2 1811.5 1152.4

As can be seen from Table 2, when the artificial skin was treated withthe compound of Example 2, the ceramide content in the artificial skinwas higher than that for PC-104. Accordingly, it can be concluded thatthe compound of Example 2 exhibits better moisturizing effect thanPC-104 by increasing ceramides.

Hereinafter, formulation examples including the pseudo-ceramide compoundaccording to the present disclosure, an isomer thereof, apharmaceutically acceptable salt thereof, a prodrug thereof, a hydratethereof or a solvate thereof will be described in detail. However, thefollowing formulation examples are for illustrative purposes only and itwill be apparent to those of ordinary skill in the art that the scope ofthe present disclosure is not limited by the examples.

Formulation Example 1 Lotion

Lotion was prepared according to a commonly employed method with thecomposition described in Table 3.

TABLE 3 Ingredients Contents (wt %) Example 1 0.1 Glycerin 3.0 Butyleneglycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 PEG 12 nonylphenyl ether 0.2 Polysorbate 80 0.4 Ethanol 10.0 Triethanolamine 0.1Antiseptic, pigment and flavor adequate Purified water balance

Formulation Example 2 Nourishing Cream

Nourishing cream was prepared according to a commonly employed methodwith the composition described in Table 4.

TABLE 4 Ingredients Contents (wt %) Example 2 2.0 Polysorbate 60 1.5Sorbitan sesquioleate 0.5 PEG 60 hydrogenated castor oil 2.0 Liquidparaffin 10.0 Squalane 5.0 Caprylic/capric triglyceride 5.0 Glycerin 5.0Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Antiseptic,pigment and flavor adequate Purified water balance

Formulation Example 3 Massage Cream

Massage cream was prepared according to a commonly employed method withthe composition described in Table 5.

TABLE 5 Ingredients Contents (wt %) Example 3 1.0 Beeswax 10.0Polysorbate 60 1.5 PEG 60 hydrogenated castor oil 2.0 Sorbitansesquioleate 0.8 Liquid paraffin 40.0 Squalane 5.0 Caprylic/caprictriglyceride 4.0 Glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0Triethanolamine 0.2 Antiseptic, pigment and flavor adequate Purifiedwater balance

Formulation Example 4 Pack

Pack was prepared according to a commonly employed method with thecomposition described in Table 6.

TABLE 6 Ingredients Contents (wt %) Example 4 0.2 Polyvinyl alcohol 13.0Sodium carboxymethylcellulose 0.2 Glycerin 5.0 Allantoin 0.1 Ethanol 6.0PEG 12 nonyl phenyl ether 0.3 Polysorbate 60 0.3 Antiseptic, pigment andflavor adequate Purified water balance

Formulation Example 5 Gel

Gel was prepared according to a commonly employed method with thecomposition described in Table 7.

TABLE 7 Ingredients Contents (wt %) Example 5 0.5 Sodiumethylenediamineacetate 0.05 Glycerin 5.0 Carboxyvinyl polymer 0.3Ethanol 5.0 PEG 60 hydrogenated castor oil 0.5 Triethanolamine 0.3Antiseptic, pigment and flavor adequate Purified water balance

Formulation Example 6 Ointment

Ointment was prepared according to a commonly employed method with thecomposition described in Table 8.

TABLE 8 Ingredients Contents (wt %) Example 6 1.5 Glycerin 8.0 Butyleneglycol 4.0 Liquid paraffin 15.0 β-Glucan 7.0 Carbomer 0.1Caprylic/capric triglyceride 3.0 Squalane 1.0 Cetearyl glucoside 1.5Sorbitan stearate 0.4 Cetearyl alcohol 1.0 Beeswax 4.0 Antiseptic,pigment and flavor adequate Purified water balance

1. A novel pseudo-ceramide compound represented by Chemical Formula 1,an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrugthereof, a hydrate thereof or a solvate thereof:

wherein each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.
 2. The novel pseudo-ceramide compound, isomer thereof,pharmaceutically acceptable salt thereof, prodrug thereof, hydratethereof or solvate thereof according to claim 1, wherein each of R₁ andR₂ is independently a C₁₁-C₁₇ saturated or unsaturated aliphatic chainunsubstituted or substituted with a hydroxyl group.
 3. The novelpseudo-ceramide compound, isomer thereof, pharmaceutically acceptablesalt thereof, prodrug thereof, hydrate thereof or solvate thereofaccording to claim 1, wherein each of R₁ and R₂ is independentlyselected from a group consisting of C₁₁H₂₃, C₁₃H₂₇, C₁₅H₃₁, C₁₇H₃₅,C₁₇H₃₁ and C₁₇H₃₃.
 4. The novel pseudo-ceramide compound, isomerthereof, pharmaceutically acceptable salt thereof, prodrug thereof,hydrate thereof or solvate thereof according to claim 1, which istris(hydroxymethyl)aminomethane substituted with a fatty acid.
 5. Thenovel pseudo-ceramide compound, isomer thereof, pharmaceuticallyacceptable salt thereof, prodrug thereof, hydrate thereof or solvatethereof according to claim 1, which is selected from a group consistingof hexadecanoic acid2-hexadecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester, dodecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,tetradecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, octadecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, octadecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,octadecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, dodecanoicacid 3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester,octadec-9-enoic acid3-hydroxy-2-hydroxymethyl-2-octadec-9-enoylamino-propyl ester,octadeca-9,12-dienoic acid3-hydroxy-2-hydroxymethyl-2-octadeca-9,12-dienoylamino-propyl ester,10-hydroxy-dec-2-enoic acid3-hydroxy-2-(10-hydroxy-dec-2-enoylamino)-2-hydroxymethyl-propyl ester,10-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(10-hydroxy-octadecanoylamino)-propyl ester,12-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(12-hydroxy-octadecanoylamino)-propyl esterand 16-hydroxy-hexadecanoic acid3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester.6. A method for preparing the novel pseudo-ceramide compound, isomerthereof, pharmaceutically acceptable salt thereof, prodrug thereof,hydrate thereof or solvate thereof according to claim 1, comprisingreacting tris(hydroxymethyl)aminomethane and a fatty acid compound undera basic condition to synthesize a pseudo-ceramide compound.
 7. Themethod for preparing the novel pseudo-ceramide compound, isomer thereof,pharmaceutically acceptable salt thereof, prodrug thereof, hydratethereof or solvate thereof according to claim 6, wherein the method isrepresented by Scheme 1:

wherein each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.
 8. The method for preparing the novel pseudo-ceramide compound,isomer thereof, pharmaceutically acceptable salt thereof, prodrugthereof, hydrate thereof or solvate thereof according to claim 7,wherein each of R₁ and R₂ is independently a C₁₁-C₁₇ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.
 9. The method for preparing the novel pseudo-ceramide compound,isomer thereof, pharmaceutically acceptable salt thereof, prodrugthereof, hydrate thereof or solvate thereof according to claim 7,wherein each of R₁ and R₂ is independently selected from a groupconsisting of C₁₁H₂₃, C₁₃H₂₇, C₁₅H₃₁, C₁₇H₃₅, C₁₇H₃₁ and C₁₇H₃₃.
 10. Acomposition for moisturizing skin, comprising the novel pseudo-ceramidecompound, isomer thereof, pharmaceutically acceptable salt thereof,prodrug thereof, hydrate thereof or solvate thereof according to claim 1as an active ingredient.
 11. The composition for moisturizing skinaccording to claim 10, wherein the active ingredient is included in anamount of 0.01-20 wt % based on the total weight of the composition. 12.The composition for moisturizing skin according to claim 10, wherein thecomposition is a composition for external application to skin.
 13. Thecomposition for moisturizing skin according to claim 10, wherein thecomposition is a cosmetic composition or a pharmaceutical composition.14. A method for moisturizing skin of a subject, comprisingadministering to the subject an effective amount of the novelpseudo-ceramide compound, isomer thereof, pharmaceutically acceptablesalt thereof, prodrug thereof, hydrate thereof or solvate thereof:

wherein each of R₁ and R₂ is independently a C₉-C₂₃ saturated orunsaturated aliphatic chain unsubstituted or substituted with a hydroxylgroup.
 15. The method according to claim 14, wherein each of R₁ and R₂is independently a C₁₁-C₁₇ saturated or unsaturated aliphatic chainunsubstituted or substituted with a hydroxyl group.
 16. The methodaccording to claim 14, wherein each of R₁ and R₂ is independentlyselected from a group consisting of C₁₁H₂₃, C₁₃H₂₇, C₁₅H₃₁, C₁₇H₃₅,C₁₇H₃₁ and C₁₇H₃₃.
 17. The method according to claim 14, wherein novelpseudo-ceramide compound, isomer thereof, pharmaceutically acceptablesalt thereof, prodrug thereof, hydrate thereof or solvate thereof istris(hydroxymethyl)aminomethane substituted with a fatty acid.
 18. Themethod according to claim 14, wherein novel pseudo-ceramide compound,isomer thereof, pharmaceutically acceptable salt thereof, prodrugthereof, hydrate thereof or solvate thereof is selected from a groupconsisting of hexadecanoic acid2-hexadecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester, dodecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,tetradecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, octadecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, octadecanoicacid 2-dodecanoylamino-3-hydroxy-2-hydroxymethyl-propyl ester,octadecanoic acid 3-hydroxy-2-hydroxymethyl-2-tetradecanoylamino-propylester, tetradecanoic acid3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester, dodecanoicacid 3-hydroxy-2-hydroxymethyl-2-octadecanoylamino-propyl ester,octadec-9-enoic acid3-hydroxy-2-hydroxymethyl-2-octadec-9-enoylamino-propyl ester,octadeca-9,12-dienoic acid3-hydroxy-2-hydroxymethyl-2-octadeca-9,12-dienoylamino-propyl ester,10-hydroxy-dec-2-enoic acid3-hydroxy-2-(10-hydroxy-dec-2-enoylamino)-2-hydroxymethyl-propyl ester,10-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(10-hydroxy-octadecanoylamino)-propyl ester,12-hydroxy-octadecanoic acid3-hydroxy-2-hydroxymethyl-2-(12-hydroxy-octadecanoylamino)-propyl esterand 16-hydroxy-hexadecanoic acid3-hydroxy-2-(16-hydroxy-hexadecanoylamino)-2-hydroxymethyl-propyl ester.